DXA R01 Project Summary The PROMISE 1077BF trial found significantly decreased Bone Mineral Density (BMD) by 18 months post delivery among asymptomatic HIV infected mothers randomized to receive antiretroviral therapy (ART) during extended breastfeeding when compared to mothers whose infants were randomized to receive nevirapine prophylaxis during breastfeeding. Breastfeeding is also associated with transient decreases in BMD but usually followed by BMD recovery. Among HIV infected women, the longer term impact of life time ART with repeat pregnancy/repeat breastfeeding on maternal BMD of HIV infected mothers remains unknown. However our initial findings from PROMISE on BMD decreases seen with ART during breastfeeding raise concerns over a potential increased risk of early osteopenia or osteoporosis when compared to mothers are not HIV infected and not exposed to lifetime ART. Given these PROMISE findings, we propose a longitudinal follow up of BMD changes with repeat pregnancy and extended breastfeeding among HIV infected mothers from the PROMISE trial who are now enrolled in the PROMOTE cohort follow up study at the Blantyre Malawi and the Kampala Uganda site, in order to better understand factors affecting both lose and recovery patterns of BMD for HIV infected women on lifetime ART. AIM 1: We will gather baseline BMD data at entry into PROMOTE and compare to prior DXA measures in PROMISE in order to assess changes clinical risk factors for low BMD in HIV Infected women AIM 2: for HIV infected women who have a repeat pregnancy during PROMOTE follow up, determine BMD loss and recovery patterns: and bone biomarker changes during 36 months follow up post delivery and compare results to age group, parity and site matched HIV negative pregnant women; AIM 3: compare BMD and bone biomarker findings with PROMOTE mothers matched for age group, parity and site but who do not conceive during 36 months of follow up. This research will elucidate whether decreases in BMD among HIV infected mothers on lifetime ART are exacerbated with repeat pregnancy/breastfeeding and if BMD recovery at the end of breastfeeding is decrease when compared to HIV negative women at the end of breastfeeding.